Atmospheric pressure ionization (API) methods have been widely used to couple chromatographic separations such as high performance liquid chromatograph (LC) or capillary electrophoresis (CE) to mass spectrometers for chemical and biochemical sample analysis. In such systems, the sample effluent from a LC, for instance, is delivered to a capillary placed near the mass spectrometer inlet or interface. By applying a potential difference between the capillary and interface, charge droplets are generated in a continuous spray. Charged droplets further undergo a desolvation process and ion species are generated for mass spectrometry analysis.
Collisions between gas molecules and solution facilitate generation of fine droplets. In nanospray techniques it has been common to use direct nebulization without a gas assist. Both pneumatic and direct nebulization methods provide relatively stable spray ionization in case sample effluent contains high concentration of organic solvent. However, for analytes having a higher water content it is typically more difficult to form stable spray in a direct nebulization source. Electrospray generated by direct nebulization also typically contains relatively large droplet which are more likely to be incompletely desolvated before entering the mass spectrometer. Consequently, high signal to noise is typically observed.